The germacrolides are a class of ten-membered ring sesquiterpenes. Elephantopin, a germacrolide isolated from Elephantopus elatus Bertol has been shown to possess significant tumor-inhibitory activity against Walker 256 intramuscular carcinosarcoma and P388 lymphocytic leukemia. It has been selected for further tumor panel evaluation by the National Cancer Institute; unfortunately, it is not readily available from natural sources. The primary objectives of the proposed research are to develop a general strategy for the enantiospecific total synthesis of germacrolides, and to evaluate in this context the utility of computerized molecular modeling conformational analysis as a tool for predicting the stereochemical outcome of transformations involving medium-sized ring systems. The key step in the proposed synthesis of these compounds involves the application of a new method for the construction of ten-membered rings. This method is based upon the use of sequential Cope-Claisen rearrangements of a 2, 3-divinylcyclohexyl silyl ketene acetal, wherein the unfavorable Cope equilibrium is shifted by a subsequent Claisen rearrangement. We have already demonstrated the feasibility of constructing cyclodecadienes by the above procedure. Furthermore, we have developed procedures for the introduction of the Alpha-substituted acrylate moiety necessary for the synthesis of germacrolides. Our continuing efforts will be directed toward completing the total synthesis of elephantopin, costunolide, tulipinolide, epitulipinolide, laurenobiolide, and vernudifloride utilizing this procedure.